This invention relates generally to an instrument for use in cryogenic treatment of portions of the human body, and more particularly to a capsule having a solid state heat exchange means therein for the cryogenic treatment of tissue.
In the treatment of human diseases, particularly cancer, it is frequently desired to eliminate neoplastic tissue. This can be accomplished by extirpative surgery or by in-situ necrosis. Surgical intervention has the disadvantage of causing substantial metastasis by allowing the release of malignant cells into healthy tissue during the procedure. In addition, there are many instances where surgery is impossible.
A number of procedures are available for in situ necrosis. Among these are radiation therapy, chemotherapy, electrocoagulation, hyperthermia, microwave radiation and hypothermia. The primary disadvantage of these procedures as they are practiced today is the severe side effects which they may induce as well as the danger of damage to healthy tissue.
Cryosurgery, i.e., the controlled destruction of tissue by freezing for the treatment of tumors, began with the use of carbon dioxide snow and iced saline on advanced tumors. Thereafter, liquid nitrogen, applied with a cotton swab, was used for the treatment of skin cancer. More recently, a closed-tip cryosurgical unit was developed, in which the temperature of the probe tip is reduced to -190.degree. C. through the circulation of liquid nitrogen through the probe tip of a vacuum insulated tube. A second technique involves the spraying of liquid nitrogen directly onto the target area. While the closed system has the advantage of a precise localized freezing point which allows for the preservation of adjacent tissue, and the open system allows maximal freezing of the target area, both systems may be used only once with respect to internal tumors, i.e. during the surgical procedure. As a result they can only be applied to superficial carcinomas without repeated surgery. Moreover, the use of a probe produces an unfocused sphere of frozen tissue which damages healthy tissue at least as much as tumor tissue when the probe is placed adjacent to the tumor. Invasion of the tumor with the probe, i.e. freezing from the inside out, produces an increased risk of metastasis comparable to extirpative surgery.
As the temperature of a biologic system is lowered, a phase change occurs as water is converted into ice. The ice crystals which are first formed are pure water, and the formation of these crystals in the liquid phase leads to an increasing solute concentration. The liquid phase persists until the freezing point of the concentrated electrolyte solution is reached e.g. -21.degree. C. (252.degree. K.) for a sodium chloride system.
Rapid cooling, e.g. at a rate faster than 100.degree. C. per minute, causes intracellular ice crystals, as the water does not have a chance to leave the cell before freezing occurs As a result of such rapid freezing, small ice crystals form in the cytoplasm nucleus and mitochondria of the cell and cause uncoupling of enzyme systems and DNA damage. Rapid heat loss, as well as the pH change caused by the increasing solute concentration, also damages cellular protein leading to the denaturation and detachment of the lipoprotein complex that comprises the cell membrane. In contrast, slow cooling e.g. 1.degree. C. to 10.degree. C. per minute allows extra cellular ice formation while the cell membrane acts as a barrier to crystal extension into the cell. In this case, cell damage is caused solely by dehydration and toxic levels of solute concentration in the cell. Thus, the more rapid the freeze, the greater the cell damage.
A second parameter which determines the extent of cell destruction is the rate of thaw. A slow or spontaneous thaw begins with the melting of microcrystals absorbing, in phase transition, an amount of heat equal to the latent heat of crystallization i.e. 80 Cal/g H.sub.2 O, lowering the temperature and allowing recrystallization to occur. Thus, the microcrystals grow in size and cause increasing physical damage to the cell. Thus, slow or spontaneous thawing provides greater cell damage. Mazur, "Cryobiology" 2:181-192, 1966.
It is generally accepted that the eutectic temperature of the solution is the minimum temperature for adequate cell destruction e.g. in a physiological sodium chloride system -21.degree. C.(252.degree. K.). However, lower temperatures are known to be more desirable and tumor control is increased by freezing tissue to at least -60.degree. C. Neel et al. "Laryngoscope", 83:1062-1071, 1973. It should be noted that there is a difference between the temperature T.sub.c on the surface of the freezing instrument and the temperature T.sub.n which is the temperature of the cell during necrosis. The difference between the T.sub.c and T.sub.n is a function of the distance from the surface of the instrument to the depth of the tissue when necrosis is to take place. It is also a function of the type of tissue treated.
One of the most important considerations in the hypothermic treatment of cancer is the vascularity of tumors and the relation of the rate of blood profusion to heat transfer. It is known that tumors have impaired blood circulation and reduced heat transfer capabilities. A tumor expands predominantly by the growth of cells at the advancing margins, where new capillaries are formed which are closely related to their conjunctive arteries and veins. Capillaries in the center of the tumor, on the other hand, are connected only to other capillaries and thus blood flow becomes quite sluggish. The application of freezing temperatures to the margin of the advancing tumor substantially diminishes the blood flow and reduces the circulatory input of heat into the target area. This reduction in heat input allows a greater volume of tissue to be frozen using repetitive freeze-thaw cycles. The cytostatic damage caused by repetitive freezes is greater than damage caused by a single freeze-thaw cycle and thus tumor control is increased.
U.S. Pat. No. 3,133,539 to Eidus describes a thermoelectric medical instrument which may be used to supply controlled cooling temperatures to the heart during surgery and for external uses such as freezing treatment of warts and skin blemishes. The instrument includes a thermocouple assembly composed of a series of semiconductor elements of the p-type, alternating with semiconductor elements of the n-type and adapted to produce cooling by the Peltier effect. The instrument of the U.S. Pat. No. 3,133,539 is of substantial size and is intended to produce a temperature approximating that of crushed ice. In fact, the maximum cooling effect at the headpiece of the instrument is disclose as being between -20.degree. C. and -25.degree. C.
U.S. Pat. No. 3,369,549 to Armao relates to a thermoelectric heat exchange capsule probe, similarly employing the Peltier effect, which may be used during surgery to freeze tumors to avoid the metastisizing for release of malignant cells into healthy tissue. Cooling of the diseased portion renders the malignant cells immobile by inhibiting the movement of fluids and cells in the tissue. It is acknowledged that freezing at sufficiently low temperatures will destroy cancer cells, but the thermoelectric instrument of the U.S. Pat. No. 3,369,549 claims only to freeze the tissue sufficiently to prohibit metastasis and the instrument is to be used as an adjunct in extirpative surgery rather than a primary instrument for cell necrosis.
Solid state cooling devices, such as those shown in the aforementioned patents, have heretofore been unable to attain the cytostatic temperatures required for cell necrosis and tumor control. The efficiency of the Peltier cooler, in terms of temperature change per unit of electric current required, decreases dramatically with colder temperatures. Even with cascaded thermoelectric coolers, -90.degree. C. from room temperature is the practical limit with the Peltier effect, and the maximum temperature difference developed across a stage is directly proportional to the square of the cold junction temperature. Thus, it is apparent that solid state cooling devices of efficacious size and current demands, while capable of providing substantial advantages over closed tip liquid nitrogen cryoprobes, have heretofore been incapable of obtaining the extreme subfreezing temperatures required for effective tumor control.